MieroRNA多态性位点与缺血性脑卒中发病风险的相关性分析

Analysis of association of genetic polymorphisms of microRNAs with ischemic stroke

目的探讨hsa-miR-196a2、hsa—miR-149、hsa—miR-146a和hsa—miR-499单核苷酸多态性与缺血性脑卒中的相关性。方法采用Taqman—PCR和DNA直接测序技术分析上述位点的基因型在来自浙江东阳地区的510例缺血性脑卒中患者和523例对照人群的频率分布，并探讨其与缺血性脑卒中的相关性。结果两组人群的临床表型比较显示，吸烟、糖尿病、高血压、肥胖、高血脂与缺血性脑卒中明显相关。hsa—miR-146a的rs2910164位点在显性遗传（P=0．012，OR=1．325，95％CI：1．110～1．580）、共显性模型（CG735．CC：P=0．002，OR-1．878，95％CI：1．269～2．789）、隐形模型（P=0．008，OR=1．630，95％CI：1．130～2．342）和等位基因模型（P=0．002，OR=1．449，95％CI：1．210～1．731）中与缺血性脑卒中明显相关。进一步分层分析显示，此位点在本地区吸烟和高血压人群中与缺血性脑卒中显著相关，而hsa—miR-196a2rs11614913、hsa-miR-149rs2292832和hsa-miR-499rs3746444位点则与此病无相关性。结论吸烟、糖尿病、高血压、肥胖和高血脂是缺血性脑卒中风险因素。hsa—miR-146ars2910164位点与浙江东阳地区吸烟和高血压人群的缺血性脑卒中的发病风险呈正相关，可能参与其发病过程，此位点的CG＋GG、GG基因型和G等位基因是该地区吸烟和高血压人群缺血性脑卒中的遗传学易感因素。

Objective To assess the association of single nucleotide polymorphisms of hsa-miR-196a2, hsa-miRq49, hsa-miR-146a, hsa-miR-499 with susceptibility to ischemic stroke. Methods Taqman-PCR and DNA sequencing assays were employed to determine the genotypes of the 4 loci among 510 patients and 523 controls. And their association with the disease was assessed. Results Analysis showed that smoking, diabetes, hypertension, BMI index and abnormal serum lipid metabolism were significantly associated with ischemic stroke, and that rs2910164 was significantly associated with the disease in codominant （CG vs. CC： P=0. 002, OR=I. 878, 95%CI=1. 269-2. 789）, dominant （P=0. 012, OR=1. 325, 95%CI=1. 110- 1.580）, recessive （P=0.008, OR=I. 630, 95%CI=1. 130-2. 342） and allele （P=0. 002, OR=1. 449, 95%CI= 1. 210-1. 731） genetic models. Stratified analysis further showed that the significant association only existed in population with smoking and hypertension. By contrast, no association was found between hsa-miR-196a2 rs11614913, hsa-miR-149 rs2292832 and hsa-miR-499 rs3746444 with the disease. Conclusion Our study indicated that smoking, diabetes, hypertension, fat and hyperlipidemia are risk factors for ischemic stroke. Hsa-miR-146a rs2910164 is significantly associated with the disease in those with smoking and hypertension in Dongyang region and may be involved in the process of the disease. The G allele G, GG and CG＋GG genotypes of the locus may underlie the susceptibility to the disease in Dongyang region.